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Jane L. Hoover-Plow, Ph.D.
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Area of general research interest:
Mechanisms of plasminogen dependent cell migration in inflammation; genetic determinants of atherothrombosis.
Current program:
- The plasminogen dependent proteoplysis and chemoattractant induction in leukocyte migration in inflammation
- Plasminogen and lipoprotein(a) interactions in the development of atherosclerosis
- Genetic determinants of atherothrombosis using C57BL/6J and A/J chromosome substitution mouse strains
- Reduction of stress ameliorates cardiovascular risk (Bakken Clinical Project)
Investigators:
- Yanqing Gong, Ph.D., Postdoctoral Fellow
- Qila Sa, Ph.D., Postdoctoral Fellow
- Tracey Schneeman, Ph.D., Postdoctoral Fellow
- Jingfeng Sha, M.D., Postdoctoral Fellow
- Erika Hart, B.S., Research Technologist
Collaborators:
- Nicholas Davidson, M.D.
- Larry Erway, Ph.D.
- Scott Heinemann, Ph.D.
- Jorge Joven, M.D.
- Malcolm Low, Ph.D.
- Lindsey Miles, Ph.D.
- Joseph Nadeau, Ph.D.
- Edward F. Plow, Ph.D.
- Jonathan Smith, Ph.D.
Brief Description:
Many studies document the association of inflammatory and hemostatic markers with cardiovascular disease (CVD), suggesting that inflammation and thrombosis are critical factors in its initiation/progression.
Studies of mice in which genes for plasminogen (Plg) and other Plg system components have been inactivated verify the crucial role of the system in clot lysis and maintenance of vascular patency in vivo. Such studies implicate Plg in several physiological and pathological processes unrelated to clot lysis; of particular relevance to the pathogenesis of CVD is inflammation.
Our data show that Plg exerts a profound effect on inflammatory cell mobilization, and we are evaluating the inflammatory response to cytokine production, cell recruitment, and extracellular matrix (ECM) remodeling, key events in the development and recovery phases of CVD. Apo(a), structurally similar to Plg, when overexpressed in mice exhibits both Plg-dependent and -independent effects in inflammatory and vascular injury models.
We have a longstanding collaboration with Joseph Nadeau, Ph.D., of Case Western Reserve University regarding Plg function in mice susceptible or resistant to atherosclerosis and thrombosis. From 21 strains screened, we identified one strain with reduced macrophage recruitment, a Plg-dependent phenotype, and three strains with genes for Plg, PAI-1, and a2-antiplasmin that have altered re-bleeding time in a tail bleeding assay.
Ongoing studies focus on identifying specific interactions of these genes that modify Plg function in inflammation and CVD.
Key References:
Simó, J.M., Joven, J., Vilella, E., Ribas, M., Pujana, M.A., Sundaram, I.M., Hammel, J.P., Hoover-Plow J.L. Impact of apolipoprotein(a) isoform size heterogeneity on the lysine binding function of lipoprotein(a) in early onset coronary artery disease. Thromb Haemost 85:412–417, 2001.
Hoover-Plow, J., Skomorovska-Prokvolit, O., Welsh, S. Selective behaviors altered in plasminogen-deficient mice are reconstituted with intracerebroventricular injection of plasminogen. Brain Res 898:256–264, 2001.
Hoover-Plow, J., Ellis, J., Yuen, L. In vivo plasminogen deficiency reduces fat accumulation. Thromb Haemost 87:1011–1019, 2001.
Oh, C.W., Hoover-Plow, J., Plow, E.F. The role of plasminogen in angiogenesis in vivo. J Thromb Haemost 1:1683–1682, 2003.
Wang, N., Zhang, L., Miles, L., Hoover-Plow, J. Plasminogen regulates pro-opiomelanocortin processing. J Thromb Haemost 2:785-796, 2004.
Plow EF, Hoover-Plow J. The functions of plasminogen in cardiovascular disease. Trends Cardiovasc Med 2004;14:180-6.
Sha, J., McCullough, B., Hart, E., Shchurin, A., Nassir, F., Davidson, N.O., Hoover-Plow, J. Apo(a) promotes thrombosis in vascular injury model by a mechanism independent of plasminogen. J Thromb Haemost 3:2281-2289. 2005.
Hoover-Plow J. Elusive proatherothrombotic role of Lp(a): a new direction? J Thromb Haemost 2006;4:971-2.
Hoover-Plow J, et al. Genetic background determines response to hemostasis and thrombosis. BMC Blood Disord 2006;DOI: 10.1186/1471-2326-6-6.